An estimated 2,100 infants will be affected by the cicatricial form of Retinopathy of Prematurity (ROP) annually in the United States, with many more cases occurring in other countries throughout the world. In 1979, the number of U.S. infants blinded by ROP was approximately 546, and the nubmer is believed to have been increasing steadily. Surgical treatment of the retinal detachments that occur in advanced stages of ROP has not proven successful. It is hypothesized that ablation of ischemic retinal tissue could minimize or terminate the perverted pre-retinal vasoproliferation, as it does in diabetic eye disease. Reports that either photo- or cryo-coagulation of the peripheral retina have some benefit have been appearing for more than 10 years, yet there have been sufficient reports of treatment failure or suspected harm to treated eyes to warrant caution in accepting cryotherapy as valid treatment. Unfortunately, none of the positive reports contain sufficient numbers of treated eyes to produce statistically valid information. Most studies are retrospective and do not randomize patients who have similar degrees of ROP. The various classification schemes used make comparison of studies impossible. It is well known that impressive stages of retinopathy can regress and leave the eye without serious sequellae, and only a small minority of eyes with ROP go on to blindness during childhood. The recently developed International Classification of ROP now permits a collaborative trial, with consistent identification of cases, enrollment of uniform stages of the disease and comparison of data among observers at different locations. The present proposal is for a randomized, prospective multicenter trial of the safety and efficacy of trans-scleral cryotherapy of the peripheral retina in certain patients with retinopathy of prematurity (ROP), in retarding progression of the acute disease to severe grades of cicatricial retrolental fibroplasia (RLF). Data on all eligible infants (birth weight less than 1251 grams, surviving 28 days) will be prospectively accumulated for descriptive analyses to identify factors in the development of ROP, such as location, extent, and presence or absence of "plus" disease (International Classification of ROP) which play a role in prognosis. An estimated 6,000 to 7,000 infants must be followed, to identify as cryotherapy candidates all infants in whom the disease progresses to a "threshold" (defined in chapter 5) severity of ROP. Approximately 80% of the estimated 300 to 400 threshold infants required to be randomized for this study are expected to have disease affecting the two eyes symmetrically. In these, one eye will receive cryotherapy and the other eye will receive no treatment, the treated eye being selected at random. The 20% asymmetrically affected threshold infants will have only the first eye reaching threshold randomly allocated to cryotherapy or control. Efficacy of cryotherapy will be judged by comparison of the treated vs. the control eyes at three months and one year of follow-up. This will be done by masked evaluation of photographs at a Photograph Reading Center.